<p>In this study, we systematically investigated the multi-scale mechanical response mechanism of red sandstone under progressive load cyclic impact at confining pressure gradient of 0–35&#xa0;MPa by combining the dynamic impact test of separate Hopkinson pressure bar and numerical simulation of finite-discrete element method. The results show that the rock damage evolution exhibits significant confining pressure regulation characteristics. With the change of confining pressure, the failure mode gradually transitions from crushing mode to block rupture mode and ultimately evolves into a shear-dominated fracture failure mode. The post-peak strength loss rate of rock is negatively correlated with confining pressure, and the loss of post-peak bearing performance is reduced to less than 15% at high confining pressure. The evolution of the broken energy of the rock sample has the characteristic of ‘step growth and quasi-static expansion.’ The peak value of the strain energy increases first and then decreases with the progress of impact, and its inflection point can be used as the instability threshold of the rock. With the increase in confining pressure, the energy distribution of the rock system shows a three-stage evolution mechanism of ‘dissipation-equilibrium-energy locking.’ There exists an optimal threshold for the inhibitory effect on crack propagation by the size of confining pressure, and the optimal confining pressure can achieve the best damage inhibition mechanism for the rock. The research results can provide theoretical basis for the stability assessment of surrounding rock and control of dynamic disasters in deep underground engineering.</p>